Top 10: September 9

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By Christian Hoffmann &
Bernd S. Kamps

9 September

Epidemiology

Gandhi M, Rutherford GW. Facial Masking for Covid-19 — Potential for “Variolation” as We Await a Vaccine. NEJM September 8, 2020. Full-text: https://doi.org/10.1056/NEJMp2026913

In this perspective, Monica Gandhi and George W. Rutherford review the growing evidence that universal facial masking might help reduce the severity of disease and ensure that a greater proportion of new infections are asymptomatic. If this hypothesis is borne out, universal masking could become a form of “variolation” (inoculation) that would generate immunity and thereby slow the spread of the virus.

 

Vaccine

Phillips N, Cyranoski D, Mallapathy S. A leading coronavirus vaccine trial is on hold: scientists react. Nature News September 9, 2020. Full-text: https://www.nature.com/articles/d41586-020-02594-w

This article summarizes what is known about the news of the day: AstraZeneca has reported a case of a transverse myelitis in a person who received AZD1222, an adenoviral-vector vaccine that harnesses a cold-causing ‘adenovirus’ isolated from chimpanzees. The Phase III trial was “voluntarily paused”. However, details of the adverse event, including how serious it was and when it happened, have not been reported. It is still unclear whether the person received the vaccine or placebo. Let’s wait for the details.

 

Shah S, Patel J, Alchaki AR. Development of Transverse Myelitis after Vaccination. A CDC/FDA Vaccine Adverse Event Reporting System (VAERS) Study, 1985–2017. Neurology April 10, 2018; 90. Abstract: https://n.neurology.org/content/90/15_Supplement/P5.099

In the meantime, you may read this review of 119 cases of transverse myelitis (TM) occurring after vaccination, reported during a period of over 30 years to the FDA. Although the reporting rate of post-vaccination TM was in the range expected in the general population, the unbalanced distribution of these cases in the first 6 weeks after vaccination suggested that the association between vaccination and some cases may not be coincidental. (For antivaxxers: this is rare!)

 

Diagnostics

Watson J, Richter A, Deeks J. Testing for SARS-CoV-2 antibodies. BMJ September 8, 2020. Full-text: https://doi.org/10.1136/bmj.m3325

This brilliant article offers an approach to antibody testing in individuals with and without symptoms suggestive of current or past SARS-CoV-2 infection. The sensitivity and specificity of antibody tests vary over time and results should be interpreted in the context of clinical history. The authors give a practical overview of the pitfalls of antibody testing and how to communicate risk and uncertainty.

 

Behrens GM, Cossmann a, Stakov MV, et al. Strategic Anti-SARS-CoV-2 Serology Testing in a Low Prevalence Setting: The COVID-19 Contact (CoCo) Study in Healthcare Professionals. Infect Dis Ther 2020 Sep 4. Full-text: https://doi.org/10.1007/s40121-020-00334-1

At Hannover Medical School, Georg Behrens and colleagues have screened 1080 samples from 217 HCP for anti-SARS CoV-2 (S1) IgG. Only one out of eight initial positive results were confirmed by alternative serology tests or showed in vitro neutralisation against live SARS-CoV-2. When assessing anti-SARS-CoV-2 immune status in individuals with low pre-test probability, it may be better to confirm positive results from single measurements by alternative serology tests or functional assays.

 

Jacobs JL, Mellors JW. Detection of SARS-CoV-2 RNA in Blood of Patients with COVID-19: What Does It Mean? Clinical Infectious Diseases, 08 September 2020- Full-text: https://doi.org/10.1093/cid/ciaa1316

Jana Jacobs and John Mellors (among the first researchers in the early 90’s who established HIV viral load as a strong predictor of progression) say: we still don’t know enough. According to this brief review, the clinical significance of SARS-CoV-2 “RNAaemia” needs to be defined.

 

Clinical

Sauer F, Dagrenat C, Couppie P, et al. Pericardial effusion in patients with COVID-19: case series. European Heart Journal 09 September 2020. Full-text: https://doi.org/10.1093/ehjcr/ytaa287

Three patients aged 51–84 developed a pericarditis related to COVID-19, associated for two of them with a myocarditis. All three were treated with colchicine and their condition improved rapidly.

 

Pregnancy

Henninghausen L, Lee HK. Activation of the SARS-CoV-2 receptor Ace2 through JAK/STAT-dependent enhancers during pregnancy. Cell Rep September 06, 2020. Full-text: https://doi.org/10.1016/j.celrep.2020.108199

The ACE2 gene is expressed in mammary tissue and activated during pregnancy and lactation through intronic enhancers built on the transcription factor STAT5.

 

Pediatrics

Consiglio CR, Cotugno N, Sardh F, et al. The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19. Cell September 06, 2020. Full-text: https://www.cell.com/cell/fulltext/S0092-8674(20)31157-0

Paper of the day, giving important insights into MIS-C. Petter Brodin, Paolo Palma, Nils Landegren, Camila Rosat Consiglio and colleagues compared 41 children with mild SARS-CoV-2 infection with 13 children presenting with MIS-C and 28 children presenting with Kawasaki disease prior to the COVID-19 pandemic. They show that inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, IL-17A and biomarkers associated with arterial damage. Finally, auto-antibody profiling suggests multiple auto-antibodies that could be involved in the pathogenesis of MIS-C.

 

Ahmed M, Advani S, Moreira A, et al. Multisystem inflammatory syndrome in children: A systematic review. EClinical Medicine September 04, 2020. Full-text: https://doi.org/10.1016/j.eclinm.2020.100527

This review included 39 observational studies with 662 MIS-C patients. While 71% of children were admitted to the intensive care unit (22% required mechanical ventilation), only 11 deaths (1.7%) were reported. Fever (100%), abdominal pain or diarrhea (74%), and vomiting (68%) were the most common clinical presentation.